1. Field of the Invention
The present invention relates to ophthalmic formulations and more particularly, ophthalmic formulations of nonsteroidal anti-inflammatory agents, particularly diclofenac sodium.
2. Description of the Related Art
Cyclooxygenase is essential in the biosynthesis of prostaglandins which have been shown in many animal models to be mediators of intraocular inflammation. Although sterioidal compounds have been used to treat such inflammation, non-steroidal anti-inflammatory agents, from the group of drugs known as cyclooxygenase inhibitors; have been substituted for steroids because they have not shown the same propensity to produce side-effects in ocular tissues as ophthalmic steroids. Non-steroidal agents are also widely prescribed to reduce pain and inflammation in a wide number of tissues. When used as topical agents in the eye, they suppress inflammatory responses and to prevent particular side-effects of surgical trauma (on the pupil preventing surgical meiosis), fluid accumulating in the back of the eye after cataract surgery (post-surgical macular edema) and the appearance of inflammatory cells and vessel leakage in the anterior chamber. Topical application of non-steroidal anti-inflammatory agents in the eye also appears to relieve some of the itching due to allergic conjunctivitis. Diclofenac sodium, suprofen, and flurbiprofin are non-steroidal anti-inflammatory agents that have been used for the treatment of postoperative inflammation in patients who have undergone cataract extraction.
Anti-inflammatory agents have in the past been administered in solutions at neutral pH. Injection of anti-inflammatory agents in the form of a suspension has also been proposed. Suspensions have been used for topical ophthalmic applications when the drug is not very soluble. However, when the drug is soluble, at an acceptable pH, solutions are usually used to avoid potential irritation caused by the particles of a suspension. The following patents illustrate ophthalmic solutions containing non-steroidal anti-inflammatory agents, including diclofenac.
U.S. Pat. No. 4,960,799 to Nagy concerns a storage stable aqueous solution of sodium ortho-(2,6-dichlorophenyl)aminophenylacetate acid, which is the chemical name for diclofenac sodium, for topical treatment of ocular inflammation. The solution taught by Nagy has a pH of about 7.0 to 7.8.
U.S. Pat. No. 4,829,083 to Doulakas relates to stabilization of mercury-containing preservatives in liquid or gel ophthalmic medicaments with addition of 2-amino-2-hydroxymethyl-1,3-propanediol or a homologue thereof.
U.S. Pat. No. 4,829,088 to Doulakas also relates to an ophthalmic medicament containing diclofenac sodium in aqueous solution. The solution contains 2-amino-2-hydroxymethyl-1,3-propanediol as a preservative.
U.S. Pat. No. 5,110,493 to Cherng-Chyi et al. relates to ophthalmic non-steroidal anti-inflammatory drug formulations containing a quaternary ammonium preservative and a non-ionic surfactant.
Most non-steroidal anti-inflammatory agents, when used in a topical solution, however, sting upon placement in the eye. The transient burning and stinging causes tearing, which in turn, washes the drug away from the eye, resulting in reduced bioavailability of the drug. The conventional solutions of non-steroidal anti-inflammatory agents generally have a pH of 7.0 to about 8.0. This pH level provides complete solubility of the drug, thereby allowing for a high concentration of the drug to be immediately available to the cornea. The high concentration of the drug on the eye aggravates the burning and stinging effects of the drug.
The present invention provides topical ophthalmic formulations containing non-steroidal anti-inflammatory agents which reduce or eliminate the stinging and burning experienced with solutions of anti-inflammatory agents. Formulations of the present invention may be useful for treatment of any condition that may be treated by a non-steroidal anti-inflammatory agent.
Accordingly, it is an object of the invention to provide novel topical ophthalmic formulations containing non-steroidal anti-inflammatory agents.
It is a further object of the invention to provide a novel method of treating the eye.